Characterization of the ATPase cycle of human ABCA1: Implications for its function as a regulator rather than an active transporter

Gergely Szakács, Thomas Langmann, Csilla Özvegy, Evelyn Orsó, Gerd Schmitz, András Váradi, Balázs Sarkadi

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

ABCA1 plays a key role in cellular cholesterol and phospholipid traffic. To explore the biochemical properties of this membrane protein we applied a Baculovirus-insect cell expression system. We found that human ABCA1 in isolated membranes showed a specific, Mg2+-dependent ATP binding but had no measurable ATPase activity. Nevertheless, conformational changes in ABCA1 could be demonstrated by nucleotide occlusion, even without arresting the catalytic cycle by phosphate-mimicking anions. Addition of potential lipid substrates or lipid acceptors (apolipoprotein A-I) did not modify the ATPase activity or nucleotide occlusion by ABCA1. Our data indicate that ATP hydrolysis by ABCA1 occurs at a very low rate, suggesting that ABCA1 may not function as an effective active transporter as previously assumed. In the light of the observed conformational changes we propose a regulatory function for human ABCA1.

Original languageEnglish
Pages (from-to)1258-1264
Number of pages7
JournalBiochemical and biophysical research communications
Volume288
Issue number5
DOIs
Publication statusPublished - Nov 16 2001

Keywords

  • ATP binding
  • ATPase activity
  • Baculovirus-insect cell expression system
  • Cholesterol and lipid metabolism
  • Human ABCA1
  • Membrane protein
  • Nucleotide occlusion

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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